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Photochemical Reaction of 7,12-Dimethylbenz[ a ]anthracene (DMBA) and Formation of DNA Covalent Adducts

View Article: PubMed Central

ABSTRACT

DMBA, 7,12-dimethylbenz[a]anthracene, is a widely studied polycyclic aromatic hydrocarbon that has long been recognized as a probable human carcinogen. It has been found that DMBA is phototoxic in bacteria as well as in animal or human cells and photomutagenic in Salmonella typhimurium strain TA102. This article tempts to explain the photochemistry and photomutagenicity mechanism. Light irradiation converts DMBA into several photoproducts including benz[a]anthracene-7,12-dione, 7-hydroxy-12-keto-7-methylbenz[a]anthracene, 7,12-epidioxy-7,12-dihydro-DMBA, 7-hydroxymethyl-12-methylbenz[a]anthracene and 12-hydroxymethyl-7-methylbenz[a]anthracene. Structures of these photoproducts have been identified by either comparison with authentic samples or by NMR/MS. At least four other photoproducts need to be assigned. Photo-irradiation of DMBA in the presence of calf thymus DNA was similarly conducted and light-induced DMBA-DNA adducts were analyzed by 32P-postlabeling/TLC, which indicates that multiple DNA adducts were formed. This indicates that formation of DNA adducts might be the source of photomutagenicity of DMBA. Metabolites obtained from the metabolism of DMBA by rat liver microsomes were reacted with calf thymus DNA and the resulting DNA adducts were analyzed by 32P-postlabeling/TLC under identical conditions. Comparison of the DNA adduct profiles indicates that the DNA adducts formed from photo-irradiation are different from the DNA adducts formed due to the reaction of DMBA metabolites with DNA. These results suggest that photo-irradiation of DMBA can lead to genotoxicity through activation pathways different from those by microsomal metabolism of DMBA.

No MeSH data available.


Related in: MedlinePlus

Autoradiogram of 32P-postlabeled nuclease P1-treated calf thymus DNA from (A) photo-irradiation of the DNA in the presence of DMBA by UVA light (14 J/cm2) and (B) the metabolite mixture from metabolism of DMBA by rat liver microsomes in the presence of calf thymus DNA.
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f8-ijerph-02-00114: Autoradiogram of 32P-postlabeled nuclease P1-treated calf thymus DNA from (A) photo-irradiation of the DNA in the presence of DMBA by UVA light (14 J/cm2) and (B) the metabolite mixture from metabolism of DMBA by rat liver microsomes in the presence of calf thymus DNA.

Mentions: Figure 8 shows the autoradiogram of 32P-postlabeled nuclease P1-treated calf thymus DNA from (A) photo-irradiation of the DNA in the presence of DMBA by UVA light (14 J/cm2) and (B) the metabolite mixture from metabolism of DMBA by rat liver microsomes in the presence of calf thymus DNA.


Photochemical Reaction of 7,12-Dimethylbenz[ a ]anthracene (DMBA) and Formation of DNA Covalent Adducts
Autoradiogram of 32P-postlabeled nuclease P1-treated calf thymus DNA from (A) photo-irradiation of the DNA in the presence of DMBA by UVA light (14 J/cm2) and (B) the metabolite mixture from metabolism of DMBA by rat liver microsomes in the presence of calf thymus DNA.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3814705&req=5

f8-ijerph-02-00114: Autoradiogram of 32P-postlabeled nuclease P1-treated calf thymus DNA from (A) photo-irradiation of the DNA in the presence of DMBA by UVA light (14 J/cm2) and (B) the metabolite mixture from metabolism of DMBA by rat liver microsomes in the presence of calf thymus DNA.
Mentions: Figure 8 shows the autoradiogram of 32P-postlabeled nuclease P1-treated calf thymus DNA from (A) photo-irradiation of the DNA in the presence of DMBA by UVA light (14 J/cm2) and (B) the metabolite mixture from metabolism of DMBA by rat liver microsomes in the presence of calf thymus DNA.

View Article: PubMed Central

ABSTRACT

DMBA, 7,12-dimethylbenz[a]anthracene, is a widely studied polycyclic aromatic hydrocarbon that has long been recognized as a probable human carcinogen. It has been found that DMBA is phototoxic in bacteria as well as in animal or human cells and photomutagenic in Salmonella typhimurium strain TA102. This article tempts to explain the photochemistry and photomutagenicity mechanism. Light irradiation converts DMBA into several photoproducts including benz[a]anthracene-7,12-dione, 7-hydroxy-12-keto-7-methylbenz[a]anthracene, 7,12-epidioxy-7,12-dihydro-DMBA, 7-hydroxymethyl-12-methylbenz[a]anthracene and 12-hydroxymethyl-7-methylbenz[a]anthracene. Structures of these photoproducts have been identified by either comparison with authentic samples or by NMR/MS. At least four other photoproducts need to be assigned. Photo-irradiation of DMBA in the presence of calf thymus DNA was similarly conducted and light-induced DMBA-DNA adducts were analyzed by 32P-postlabeling/TLC, which indicates that multiple DNA adducts were formed. This indicates that formation of DNA adducts might be the source of photomutagenicity of DMBA. Metabolites obtained from the metabolism of DMBA by rat liver microsomes were reacted with calf thymus DNA and the resulting DNA adducts were analyzed by 32P-postlabeling/TLC under identical conditions. Comparison of the DNA adduct profiles indicates that the DNA adducts formed from photo-irradiation are different from the DNA adducts formed due to the reaction of DMBA metabolites with DNA. These results suggest that photo-irradiation of DMBA can lead to genotoxicity through activation pathways different from those by microsomal metabolism of DMBA.

No MeSH data available.


Related in: MedlinePlus